ES2731823T3 - Derivados de amida para el agonista del GPR119 - Google Patents

Derivados de amida para el agonista del GPR119 Download PDF

Info

Publication number: ES2731823T3
Authority: ES; Spain
Prior art keywords: piperidine; methoxy; carboxamide; fluoro; hydroxypyrrolidine
Prior art date: 2013-11-26
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES14866648T

Other languages

English (en)

Spanish (es)

Inventor

Yuntae Kim

Changsik Lee

Daekyu Choi

Moosung Ko

Younghue Han

Soyoung Kim

Jaeki Min

Dohoon Kim

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Chong Kun Dang Corp

Original Assignee

Chong Kun Dang Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2013-11-26

Filing date

2014-11-25

Publication date

2019-11-19

2014-11-25 Application filed by Chong Kun Dang Corp filed Critical Chong Kun Dang Corp

2019-11-19 Application granted granted Critical

2019-11-19 Publication of ES2731823T3 publication Critical patent/ES2731823T3/es

Status Active legal-status Critical Current

2034-11-25 Anticipated expiration legal-status Critical

Links

150000001408 amides Chemical class 0.000 title claims abstract description 25
AJJISMLYIMQAKP-OAHLLOKOSA-N 5-[4-[(2r)-4-(3-fluoro-4-methylsulfonylphenoxy)butan-2-yl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(CC2)[C@H](C)CCOC=2C=C(F)C(=CC=2)S(C)(=O)=O)=N1 AJJISMLYIMQAKP-OAHLLOKOSA-N 0.000 title claims description 5
229940100607 GPR119 agonist Drugs 0.000 title claims description 5
-1 (1 - ((1- (trifluoromethyl) cyclobutyl) methyl) piperidine-4-yl) methoxy Chemical group 0.000 claims abstract description 259
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 105
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 80
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 64
150000003839 salts Chemical class 0.000 claims abstract description 32
229910052736 halogen Inorganic materials 0.000 claims abstract description 28
150000002367 halogens Chemical class 0.000 claims abstract description 28
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 20
VLJNHYLEOZPXFW-UHFFFAOYSA-N pyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1 VLJNHYLEOZPXFW-UHFFFAOYSA-N 0.000 claims abstract description 16
229910052799 carbon Inorganic materials 0.000 claims abstract description 11
NKLYVCPMMWKOTK-RLWLMLJZSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F NKLYVCPMMWKOTK-RLWLMLJZSA-N 0.000 claims abstract description 7
150000001721 carbon Chemical group 0.000 claims abstract description 7
OZAZXPYTQNNGFK-QPPBQGQZSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N OZAZXPYTQNNGFK-QPPBQGQZSA-N 0.000 claims abstract description 6
GEDGOYSBBTZKPG-CZWSTGFNSA-N (2S,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC1)(C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N)F)(CC)F GEDGOYSBBTZKPG-CZWSTGFNSA-N 0.000 claims abstract description 6
CQNIDDUGELWDSD-KCWPFWIISA-N (2S,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N)(CC)F CQNIDDUGELWDSD-KCWPFWIISA-N 0.000 claims abstract description 6
JQHFYBKPNAUARN-OFNKIYASSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C JQHFYBKPNAUARN-OFNKIYASSA-N 0.000 claims abstract description 6
MZWYKVKIBULCQG-GCJKJVERSA-N (2S,4R)-1-[2-fluoro-6-[4-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=CC=C1)C1=CC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N MZWYKVKIBULCQG-GCJKJVERSA-N 0.000 claims abstract description 6
LCSDJVHNINVYTD-YKSBVNFPSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=NC(=NC1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F LCSDJVHNINVYTD-YKSBVNFPSA-N 0.000 claims abstract description 6
125000000217 alkyl group Chemical group 0.000 claims abstract description 6
GEDGOYSBBTZKPG-JRSXUWQBSA-N (2R,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC1)(C(=O)N1[C@H](C[C@H](C1)O)C(=O)N)F)(CC)F GEDGOYSBBTZKPG-JRSXUWQBSA-N 0.000 claims abstract description 5
OQZWGSBSYFDEEN-NLFFAJNJSA-N (2S,4R)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N OQZWGSBSYFDEEN-NLFFAJNJSA-N 0.000 claims abstract description 5
OFPRAAREYZLWJB-RDGATRHJSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=CC=CC1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N OFPRAAREYZLWJB-RDGATRHJSA-N 0.000 claims abstract description 5
LIMLIOLTRBZZOA-VGSWGCGISA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F LIMLIOLTRBZZOA-VGSWGCGISA-N 0.000 claims abstract description 5
CYBVBXICIDHGSV-XXBNENTESA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F CYBVBXICIDHGSV-XXBNENTESA-N 0.000 claims abstract description 5
IOOPNHMWEMBOCV-RLWLMLJZSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-3-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=C(C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F IOOPNHMWEMBOCV-RLWLMLJZSA-N 0.000 claims abstract description 5
BQHSNFJVTVGPCI-OFNKIYASSA-N (2S,4R)-1-[4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F BQHSNFJVTVGPCI-OFNKIYASSA-N 0.000 claims abstract description 5
DHTYMFQWSPOWTF-RDGATRHJSA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F DHTYMFQWSPOWTF-RDGATRHJSA-N 0.000 claims abstract description 5
DMZCGDNJMHFSCR-RPBOFIJWSA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)(CC)F DMZCGDNJMHFSCR-RPBOFIJWSA-N 0.000 claims abstract description 5
YRZOIXCPYZEUKK-BVAGGSTKSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(CC)(F)CC)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N YRZOIXCPYZEUKK-BVAGGSTKSA-N 0.000 claims abstract description 4
FJFKJVUJCQNRPU-DVECYGJZSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C FJFKJVUJCQNRPU-DVECYGJZSA-N 0.000 claims abstract description 4
JYNXPHHATOZOJR-NLFFAJNJSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F JYNXPHHATOZOJR-NLFFAJNJSA-N 0.000 claims abstract description 4
BZXKMDYEBFGWKH-QPPBQGQZSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F BZXKMDYEBFGWKH-QPPBQGQZSA-N 0.000 claims abstract description 4
OFRWTSDWAANLDL-VGSWGCGISA-N (2S,4R)-1-[3-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F OFRWTSDWAANLDL-VGSWGCGISA-N 0.000 claims abstract description 4
CLBUANMFCJHLFX-RDGATRHJSA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-3-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=C(C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)F)(CC)F CLBUANMFCJHLFX-RDGATRHJSA-N 0.000 claims abstract description 4
KIEVEKHGLJYLAL-QPPBQGQZSA-N (2S,4R)-1-[3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F KIEVEKHGLJYLAL-QPPBQGQZSA-N 0.000 claims abstract description 3
BFZPYNZHHWFLFR-UHFFFAOYSA-N 1-hydroxypyrrolidine-2-carboxamide Chemical compound NC(=O)C1CCCN1O BFZPYNZHHWFLFR-UHFFFAOYSA-N 0.000 claims abstract 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
206010012601 diabetes mellitus Diseases 0.000 claims description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
AFPKPVGMMLNSED-DVECYGJZSA-N (2S,4R)-1-[3-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C AFPKPVGMMLNSED-DVECYGJZSA-N 0.000 claims description 6
201000010099 disease Diseases 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
AUBVCQAVMLBGBA-KOSHJBKYSA-N (2S,4R)-1-[2-fluoro-6-[2-fluoro-4-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C=CC(=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)N AUBVCQAVMLBGBA-KOSHJBKYSA-N 0.000 claims description 4
LXRUDSRTBHXMKW-MNNSJKJDSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)F)(CC)F LXRUDSRTBHXMKW-MNNSJKJDSA-N 0.000 claims description 4
MSLGZWGSOARYCO-NDEPHWFRSA-N (2s)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CC=C(C=2C=C(F)C(C(=O)N3[C@](CCC3)(C)C(N)=O)=CC=2)N=C1 MSLGZWGSOARYCO-NDEPHWFRSA-N 0.000 claims description 4
OEZCFAIKPVTJPP-PMERELPUSA-N (2S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](CCC1)(C(=O)N)C OEZCFAIKPVTJPP-PMERELPUSA-N 0.000 claims description 3
OWOJQYAGQCYCJQ-PMERELPUSA-N (2S)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](CCC1)(C(=O)N)C OWOJQYAGQCYCJQ-PMERELPUSA-N 0.000 claims description 3
JVOWWOYNBNJRJH-MHZLTWQESA-N (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=N1)OCC1CCN(CC1)CC(C)(C)F JVOWWOYNBNJRJH-MHZLTWQESA-N 0.000 claims description 3
AJMGFQCAPWOQFY-PIKZIKFNSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F AJMGFQCAPWOQFY-PIKZIKFNSA-N 0.000 claims description 3
IWYOTXJJAVEZAF-BVAGGSTKSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=C1)(CC)F IWYOTXJJAVEZAF-BVAGGSTKSA-N 0.000 claims description 3
208000030159 metabolic disease Diseases 0.000 claims description 3
DFEOSUGIUZLMBC-YKGWIAGDSA-N (2R,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@](C[C@H](C1)O)(C(=O)N)C DFEOSUGIUZLMBC-YKGWIAGDSA-N 0.000 claims description 2
XCEPJRUHUZQHCE-VWLOTQADSA-N (2S)-1-[2-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F XCEPJRUHUZQHCE-VWLOTQADSA-N 0.000 claims description 2
MVQBFLZQZYHJST-VWLOTQADSA-N (2S)-1-[3-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F MVQBFLZQZYHJST-VWLOTQADSA-N 0.000 claims description 2
HLRVESUUZAJCMZ-LJAQVGFWSA-N (2S)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=C1)F)(CC)F HLRVESUUZAJCMZ-LJAQVGFWSA-N 0.000 claims description 2
DFEOSUGIUZLMBC-RCRUUEGKSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)N)C DFEOSUGIUZLMBC-RCRUUEGKSA-N 0.000 claims description 2
VYQKLTJBYVSQAQ-NGOKVRLYSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C)(C)F VYQKLTJBYVSQAQ-NGOKVRLYSA-N 0.000 claims description 2
XCOOKCBBWXGEHN-NGOKVRLYSA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C XCOOKCBBWXGEHN-NGOKVRLYSA-N 0.000 claims description 2
BRIIVKRLAJNCJN-PIKZIKFNSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C BRIIVKRLAJNCJN-PIKZIKFNSA-N 0.000 claims description 2
VTNXFSRMYVYBPH-MNNSJKJDSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-3-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=C(C=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)F)(CC)F VTNXFSRMYVYBPH-MNNSJKJDSA-N 0.000 claims description 2
LZMAQARFMZZTRU-GIGWZHCTSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)(CC)F LZMAQARFMZZTRU-GIGWZHCTSA-N 0.000 claims description 2
HYKXWDZRCRYNCN-IRPSRAIASA-N (2S,4R)-1-[4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=C1)(CC)F HYKXWDZRCRYNCN-IRPSRAIASA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
QXTDHLPYNDPQBT-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C QXTDHLPYNDPQBT-NDEPHWFRSA-N 0.000 claims 1
BPSXABNONWEDDH-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F BPSXABNONWEDDH-NDEPHWFRSA-N 0.000 claims 1
UBEBWEZASMMAOZ-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F UBEBWEZASMMAOZ-NDEPHWFRSA-N 0.000 claims 1
DLVOZIGFZPAJLD-NDEPHWFRSA-N (2S)-1-[3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC1C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F DLVOZIGFZPAJLD-NDEPHWFRSA-N 0.000 claims 1
VKCGFMPWZWGGLO-DFXYEROKSA-N (2S,4R)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)N)C VKCGFMPWZWGGLO-DFXYEROKSA-N 0.000 claims 1
SCMVCTBFQOMYES-DFHRPNOPSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F SCMVCTBFQOMYES-DFHRPNOPSA-N 0.000 claims 1
IIXOJZCNRQAQIQ-DFHRPNOPSA-N (2S,4R)-1-[3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC1C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F IIXOJZCNRQAQIQ-DFHRPNOPSA-N 0.000 claims 1
CWYJVAWNERNGBC-XCZPVHLTSA-N (2S,3S)-1-[2-[2-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(CC)(F)CC)C=1C(=C(C=CC1)F)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N CWYJVAWNERNGBC-XCZPVHLTSA-N 0.000 abstract description 3
JEBNKEQXWUUHOV-IGKIAQTJSA-N (2S,3S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-3-fluorophenyl]-6-fluorobenzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=C(C=C(C=C1)C=1C(=C(C=CC1)F)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N)F)(CC)F JEBNKEQXWUUHOV-IGKIAQTJSA-N 0.000 abstract description 3
VDDFYQSPTNHOLY-CPJSRVTESA-N (2S,4S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)N VDDFYQSPTNHOLY-CPJSRVTESA-N 0.000 abstract description 3
IUYIFMVJWPVRGH-PMWNSHPQSA-N (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-fluoropyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC1)(C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)N)F)(CC)F IUYIFMVJWPVRGH-PMWNSHPQSA-N 0.000 abstract description 3
GYUJAJCZWAMFQX-CXBRBUDWSA-N (2S,3S)-1-[1-fluoro-2-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]cyclohexa-2,4-diene-1-carbonyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound FC1(C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N GYUJAJCZWAMFQX-CXBRBUDWSA-N 0.000 abstract description 2
DRUOOQCZVQUGDG-SVBPBHIXSA-N (2S,3S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-2-fluorophenyl]benzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC(=C(C=C1)C=1C(=CC=CC1)C(=O)N1[C@@H]([C@H](CC1)O)C(=O)N)F)(CC)F DRUOOQCZVQUGDG-SVBPBHIXSA-N 0.000 abstract description 2
QYKAWRPGYZBFEG-NLFFAJNJSA-N (2S,4R)-1-[3-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)N)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F QYKAWRPGYZBFEG-NLFFAJNJSA-N 0.000 abstract description 2
KLLRIYYOHXYLOY-NVQXNPDNSA-N (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxamide Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)N)(CC)F KLLRIYYOHXYLOY-NVQXNPDNSA-N 0.000 abstract description 2
CKQBQURWPCKBJC-UHFFFAOYSA-N 1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypiperidine-2-carboxamide Chemical compound FC1=C(C(=O)N2C(CC(CC2)O)C(=O)N)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F CKQBQURWPCKBJC-UHFFFAOYSA-N 0.000 abstract description 2
JDBDYJQOYOWMRS-UPVQGACJSA-N (2S,3S)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@H]([C@H](CC2)O)C(=O)N)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F JDBDYJQOYOWMRS-UPVQGACJSA-N 0.000 abstract 1
FLDXRNWTHKTVAP-UPVQGACJSA-N (2S,3S)-1-[3-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H]([C@H](CC2)O)C(=O)N)C=CC1C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F FLDXRNWTHKTVAP-UPVQGACJSA-N 0.000 abstract 1
VWTQILGJBLJZKY-ZCYQVOJMSA-N (2S,3S)-1-[3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-3-hydroxypyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@H]([C@H](CC2)O)C(=O)N)C=CC1C=1C=NC(=CC1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F VWTQILGJBLJZKY-ZCYQVOJMSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 559
150000001875 compounds Chemical class 0.000 description 421
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 309
239000000203 mixture Substances 0.000 description 296
239000007787 solid Substances 0.000 description 290
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 277
229910001868 water Inorganic materials 0.000 description 277
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 262
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 258
230000015572 biosynthetic process Effects 0.000 description 255
238000003786 synthesis reaction Methods 0.000 description 255
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 249
239000011541 reaction mixture Substances 0.000 description 231
235000019439 ethyl acetate Nutrition 0.000 description 198
239000012141 concentrate Substances 0.000 description 186
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 180
239000000243 solution Substances 0.000 description 175
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 166
239000007864 aqueous solution Substances 0.000 description 153
239000012044 organic layer Substances 0.000 description 136
229910052943 magnesium sulfate Inorganic materials 0.000 description 131
235000019341 magnesium sulphate Nutrition 0.000 description 131
238000004440 column chromatography Methods 0.000 description 123
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 116
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 106
238000006243 chemical reaction Methods 0.000 description 101
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 87
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 83
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 76
229910052681 coesite Inorganic materials 0.000 description 74
229910052906 cristobalite Inorganic materials 0.000 description 74
239000000377 silicon dioxide Substances 0.000 description 74
235000012239 silicon dioxide Nutrition 0.000 description 74
229910052682 stishovite Inorganic materials 0.000 description 74
229910052905 tridymite Inorganic materials 0.000 description 74
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 72
238000001914 filtration Methods 0.000 description 66
239000002904 solvent Substances 0.000 description 65
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 64
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 54
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 52
229910000041 hydrogen chloride Inorganic materials 0.000 description 52
230000005855 radiation Effects 0.000 description 49
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 42
238000000746 purification Methods 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 37
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 37
239000000047 product Substances 0.000 description 37
238000005160 1H NMR spectroscopy Methods 0.000 description 36
229910000024 caesium carbonate Inorganic materials 0.000 description 33
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
239000007821 HATU Substances 0.000 description 30
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 28
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 26
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 24
239000012230 colorless oil Substances 0.000 description 23
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 23
235000019270 ammonium chloride Nutrition 0.000 description 22
239000003643 water by type Substances 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 19
239000000706 filtrate Substances 0.000 description 19
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 19
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 17
NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 description 16
239000003921 oil Substances 0.000 description 16
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 15
DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 15
CXSPPZZTTSHTMP-UHFFFAOYSA-N (4-ethoxycarbonyl-3-fluorophenyl)boronic acid Chemical compound CCOC(=O)C1=CC=C(B(O)O)C=C1F CXSPPZZTTSHTMP-UHFFFAOYSA-N 0.000 description 14
235000015320 potassium carbonate Nutrition 0.000 description 14
229910000027 potassium carbonate Inorganic materials 0.000 description 14
238000003756 stirring Methods 0.000 description 14
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
101100485158 Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720) wzzE gene Proteins 0.000 description 13
101150089110 metN gene Proteins 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
102100033839 Glucose-dependent insulinotropic receptor Human genes 0.000 description 11
101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 description 11
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 11
KLZOTDOJMRMLDX-YBBVPDDNSA-N (1r,3s,5z)-5-[(2e)-2-[(1s,3as,7as)-1-[(1r)-1-(4-ethyl-4-hydroxyhexoxy)ethyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](C)OCCCC(O)(CC)CC)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C KLZOTDOJMRMLDX-YBBVPDDNSA-N 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 9
KLGSHNXEUZOKHH-JBUOLDKXSA-N hydron;methyl (2s,4r)-4-hydroxypyrrolidine-2-carboxylate;chloride Chemical compound Cl.COC(=O)[C@@H]1C[C@@H](O)CN1 KLGSHNXEUZOKHH-JBUOLDKXSA-N 0.000 description 9
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 9
RXNQBVRCZIYUJK-UHFFFAOYSA-N tert-butyl 4-(methylsulfonyloxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(COS(C)(=O)=O)CC1 RXNQBVRCZIYUJK-UHFFFAOYSA-N 0.000 description 9
KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 description 8
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
230000000694 effects Effects 0.000 description 7
HTJXCQYXFPTUOW-IMJSIDKUSA-N (2s,3s)-3-hydroxypyrrolidine-2-carboxamide Chemical compound NC(=O)[C@H]1NCC[C@@H]1O HTJXCQYXFPTUOW-IMJSIDKUSA-N 0.000 description 6
GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
229910013596 LiOH—H2O Inorganic materials 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
238000006069 Suzuki reaction reaction Methods 0.000 description 6
239000010410 layer Substances 0.000 description 6
AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 6
VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
208000001072 type 2 diabetes mellitus Diseases 0.000 description 6
239000007832 Na2SO4 Substances 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
RJNZZSGFHBQIIJ-UHFFFAOYSA-N ethyl 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]-2-fluorobenzoate Chemical compound C1=C(F)C(C(=O)OCC)=CC=C1C(N=C1)=NC=C1OCC1CCN(CC(F)(CC)CC)CC1 RJNZZSGFHBQIIJ-UHFFFAOYSA-N 0.000 description 5
PGEIOIOBHIGEMT-WHFBIAKZSA-N methyl (2s,4s)-4-fluoropyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1C[C@H](F)CN1 PGEIOIOBHIGEMT-WHFBIAKZSA-N 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
238000010898 silica gel chromatography Methods 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
QHZUUSNAUOEJBB-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropyl trifluoromethanesulfonate Chemical compound FC(F)(F)C(F)(F)COS(=O)(=O)C(F)(F)F QHZUUSNAUOEJBB-UHFFFAOYSA-N 0.000 description 4
MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 4
QMVROIWIZBEHPO-UHFFFAOYSA-N 2-iodo-5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazine Chemical compound C1CC(COC=2N=CC(I)=NC=2)CCN1CC1(C(F)(F)F)CCC1 QMVROIWIZBEHPO-UHFFFAOYSA-N 0.000 description 4
KGNYILKFGLORQN-UHFFFAOYSA-N 4-[(4-bromophenoxy)methyl]piperidine;hydrochloride Chemical compound Cl.C1=CC(Br)=CC=C1OCC1CCNCC1 KGNYILKFGLORQN-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
102000004877 Insulin Human genes 0.000 description 4
108090001061 Insulin Proteins 0.000 description 4
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 4
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000003814 drug Substances 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
229940125396 insulin Drugs 0.000 description 4
229910052751 metal Inorganic materials 0.000 description 4
239000002184 metal Substances 0.000 description 4
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
CCNBDZFBJCGDIV-ZETCQYMHSA-N methyl (2s)-2-methylpyrrolidine-2-carboxylate Chemical compound COC(=O)[C@]1(C)CCCN1 CCNBDZFBJCGDIV-ZETCQYMHSA-N 0.000 description 4
ZORHSASAYVIBLY-UHNVWZDZSA-N methyl (2s,4r)-4-hydroxypyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@H]1C[C@@H](O)CN1 ZORHSASAYVIBLY-UHNVWZDZSA-N 0.000 description 4
HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
CTEDVGRUGMPBHE-UHFFFAOYSA-N tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CO)CC1 CTEDVGRUGMPBHE-UHFFFAOYSA-N 0.000 description 4
BKWRLCIYMAYFPA-UHFFFAOYSA-N (2-fluoro-4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C(F)=C1 BKWRLCIYMAYFPA-UHFFFAOYSA-N 0.000 description 3
YZYGXFXSMDUXJT-UHFFFAOYSA-N (3-fluoro-4-methoxycarbonylphenyl)boronic acid Chemical compound COC(=O)C1=CC=C(B(O)O)C=C1F YZYGXFXSMDUXJT-UHFFFAOYSA-N 0.000 description 3
HYRCPSRIIWIESW-UHFFFAOYSA-N 1-(trifluoromethyl)cyclobutane-1-carboxylic acid Chemical compound OC(=O)C1(C(F)(F)F)CCC1 HYRCPSRIIWIESW-UHFFFAOYSA-N 0.000 description 3
AQHFNXWYSGTWIU-UHFFFAOYSA-N 2-bromo-5-(piperidin-4-ylmethoxy)benzonitrile;hydrochloride Chemical compound Cl.C1=C(C#N)C(Br)=CC=C1OCC1CCNCC1 AQHFNXWYSGTWIU-UHFFFAOYSA-N 0.000 description 3
VMFSJVUPIXOCFO-UHFFFAOYSA-N 3,3,3-trifluoro-2,2-dimethylpropanoic acid Chemical compound OC(=O)C(C)(C)C(F)(F)F VMFSJVUPIXOCFO-UHFFFAOYSA-N 0.000 description 3
LJVIXCOBAUVUHN-UHFFFAOYSA-N 5-bromo-2-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CC=C(Br)C=C1C#N LJVIXCOBAUVUHN-UHFFFAOYSA-N 0.000 description 3
ZBPNYTPXDPJRAK-UHFFFAOYSA-N 5-bromo-2-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridine Chemical compound C1CC(COC=2N=CC(Br)=CC=2)CCN1CC1(C(F)(F)F)CCC1 ZBPNYTPXDPJRAK-UHFFFAOYSA-N 0.000 description 3
PTEFNEALEPSHLC-UHFFFAOYSA-N 6-bromopyridin-3-ol Chemical compound OC1=CC=C(Br)N=C1 PTEFNEALEPSHLC-UHFFFAOYSA-N 0.000 description 3
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
241000282412 Homo Species 0.000 description 3
VLJNHYLEOZPXFW-BYPYZUCNSA-N L-prolinamide Chemical compound NC(=O)[C@@H]1CCCN1 VLJNHYLEOZPXFW-BYPYZUCNSA-N 0.000 description 3
XCFQDXBFLMKWJA-UHFFFAOYSA-N [1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methanol Chemical compound FC(C(CN1CCC(CC1)CO)(C)C)(F)F XCFQDXBFLMKWJA-UHFFFAOYSA-N 0.000 description 3
QZNICYWVMCAMGW-UHFFFAOYSA-N [1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methanol Chemical compound C1CC(CO)CCN1CC1(C(F)(F)F)CCC1 QZNICYWVMCAMGW-UHFFFAOYSA-N 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 3
229910000085 borane Inorganic materials 0.000 description 3
150000001639 boron compounds Chemical class 0.000 description 3
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
238000002483 medication Methods 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
235000017550 sodium carbonate Nutrition 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
UEVWLMZFMCHFOK-UTYLNVFUSA-N (2S,4R)-1-[1-fluoro-2-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]cyclohexa-2,4-diene-1-carbonyl]-4-hydroxy-2-methylpyrrolidine-2-carboxylic acid Chemical compound FC1(C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)O)C UEVWLMZFMCHFOK-UTYLNVFUSA-N 0.000 description 2
XFBUCHVPTZQNCH-VFEGMVRJSA-N (2S,4R)-1-[1-fluoro-2-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]cyclohexa-2,4-diene-1-carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound FC1(C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)O XFBUCHVPTZQNCH-VFEGMVRJSA-N 0.000 description 2
KKJALEWFJHABKM-KCWPFWIISA-N (2S,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)O)(CC)F KKJALEWFJHABKM-KCWPFWIISA-N 0.000 description 2
CWPGEBXVYVDOHV-YKSBVNFPSA-N (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound C(C)C(CN1CCC(CC1)COC=1C=NC(=NC1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)O)C=C1)F)(CC)F CWPGEBXVYVDOHV-YKSBVNFPSA-N 0.000 description 2
KALNEIIIWDPBCX-OFNKIYASSA-N (2S,4R)-1-[4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)O)C=C1)F)(CC)F KALNEIIIWDPBCX-OFNKIYASSA-N 0.000 description 2
UBIGNVXJOKIURQ-GJZUVCINSA-N (2S,4R)-4-hydroxy-1-[2-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]benzoyl]pyrrolidine-2-carboxylic acid Chemical compound O[C@@H]1C[C@H](N(C1)C(=O)C=1C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)O UBIGNVXJOKIURQ-GJZUVCINSA-N 0.000 description 2
LXTYQNVSJNDCIC-PMWNSHPQSA-N (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-fluoropyrrolidine-2-carboxylic acid Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC1)(C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)O)F)(CC)F LXTYQNVSJNDCIC-PMWNSHPQSA-N 0.000 description 2
LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
GISFRDFJIMQCIN-UHFFFAOYSA-N 1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidine Chemical compound CC(C)(CN1CCCCC1)C(F)(F)F GISFRDFJIMQCIN-UHFFFAOYSA-N 0.000 description 2
PFWFSUOSVTVZOT-FZKQIMNGSA-N 1-o-tert-butyl 2-o-methyl (2r,4r)-4-[tert-butyl(dimethyl)silyl]oxy-2-methylpyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@]1(C)C[C@@H](O[Si](C)(C)C(C)(C)C)CN1C(=O)OC(C)(C)C PFWFSUOSVTVZOT-FZKQIMNGSA-N 0.000 description 2
CTBPJCTYTFHHRY-PRHODGIISA-N 1-o-tert-butyl 2-o-methyl (2r,4r)-4-hydroxy-2-methylpyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@]1(C)C[C@@H](O)CN1C(=O)OC(C)(C)C CTBPJCTYTFHHRY-PRHODGIISA-N 0.000 description 2
PFWFSUOSVTVZOT-ACJLOTCBSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-[tert-butyl(dimethyl)silyl]oxy-2-methylpyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@]1(C)C[C@@H](O[Si](C)(C)C(C)(C)C)CN1C(=O)OC(C)(C)C PFWFSUOSVTVZOT-ACJLOTCBSA-N 0.000 description 2
GDGVOGGJKRMIOF-OLZOCXBDSA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-[tert-butyl(dimethyl)silyl]oxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@@H](O[Si](C)(C)C(C)(C)C)CN1C(=O)OC(C)(C)C GDGVOGGJKRMIOF-OLZOCXBDSA-N 0.000 description 2
CTBPJCTYTFHHRY-PELKAZGASA-N 1-o-tert-butyl 2-o-methyl (2s,4r)-4-hydroxy-2-methylpyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@]1(C)C[C@@H](O)CN1C(=O)OC(C)(C)C CTBPJCTYTFHHRY-PELKAZGASA-N 0.000 description 2
URXZQUSGSAORPL-UHFFFAOYSA-N 2-bromo-5-(pyridin-4-ylmethoxy)pyridine hydrochloride Chemical compound Cl.BrC1=NC=C(C=C1)OCC1=CC=NC=C1 URXZQUSGSAORPL-UHFFFAOYSA-N 0.000 description 2
GPGILVDNOFIDQB-UHFFFAOYSA-N 2-bromo-5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridine Chemical compound BrC1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F GPGILVDNOFIDQB-UHFFFAOYSA-N 0.000 description 2
HLKHJCFVGWDOEE-UHFFFAOYSA-N 2-bromo-5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(Br)C(C#N)=C1 HLKHJCFVGWDOEE-UHFFFAOYSA-N 0.000 description 2
PGMQNLWZBOUYMY-UHFFFAOYSA-N 2-bromo-5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridine Chemical compound BrC1=NC=C(C=C1)OCC1CCN(CC1)CC(CC)(F)CC PGMQNLWZBOUYMY-UHFFFAOYSA-N 0.000 description 2
AODZBCVWIRJALX-UHFFFAOYSA-N 2-bromo-5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CC=C(Br)C(C#N)=C1 AODZBCVWIRJALX-UHFFFAOYSA-N 0.000 description 2
SYLVRWVTNNMQHA-UHFFFAOYSA-N 2-chloro-5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyrimidine Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CN=C(Cl)N=C1 SYLVRWVTNNMQHA-UHFFFAOYSA-N 0.000 description 2
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
FZLMSGQYQLPQMN-UHFFFAOYSA-N 3-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound FC=1C=C(C(=O)O)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F FZLMSGQYQLPQMN-UHFFFAOYSA-N 0.000 description 2
ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 2
JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 2
RNLMPDZKJOJVPT-UHFFFAOYSA-N 4-[(4-bromo-2-fluorophenoxy)methyl]-1-(2-ethyl-2-fluorobutyl)piperidine Chemical compound BrC1=CC(=C(OCC2CCN(CC2)CC(CC)(F)CC)C=C1)F RNLMPDZKJOJVPT-UHFFFAOYSA-N 0.000 description 2
MDGKYIWGQJQQAI-UHFFFAOYSA-N 4-[(4-bromo-3-fluorophenoxy)methyl]-1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidine Chemical compound BrC1=C(C=C(OCC2CCN(CC2)CC(C(F)(F)F)(C)C)C=C1)F MDGKYIWGQJQQAI-UHFFFAOYSA-N 0.000 description 2
ZEMRVHKORRZGRG-UHFFFAOYSA-N 4-[(4-bromo-3-fluorophenoxy)methyl]piperidine;hydrochloride Chemical compound Cl.C1=C(Br)C(F)=CC(OCC2CCNCC2)=C1 ZEMRVHKORRZGRG-UHFFFAOYSA-N 0.000 description 2
KLCRIFSMGDACOH-UHFFFAOYSA-N 4-[(4-bromophenoxy)methyl]-1-(2,2,3,3,3-pentafluoropropyl)piperidine Chemical compound BrC1=CC=C(OCC2CCN(CC2)CC(C(F)(F)F)(F)F)C=C1 KLCRIFSMGDACOH-UHFFFAOYSA-N 0.000 description 2
NRPNTTHBSOSZGG-UHFFFAOYSA-N 4-[(4-bromophenoxy)methyl]-1-(2-ethyl-2-fluorobutyl)piperidine Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(Br)C=C1 NRPNTTHBSOSZGG-UHFFFAOYSA-N 0.000 description 2
YHMVXBDREILMSE-UHFFFAOYSA-N 4-[(4-bromophenoxy)methyl]-1-(2-fluoro-2-methylbutyl)piperidine Chemical compound BrC1=CC=C(OCC2CCN(CC2)CC(CC)(F)C)C=C1 YHMVXBDREILMSE-UHFFFAOYSA-N 0.000 description 2
OPCPFOCSMBITTL-UHFFFAOYSA-N 4-[(4-bromophenoxy)methyl]-1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidine Chemical compound C1CC(COC=2C=CC(Br)=CC=2)CCN1CC1(C(F)(F)F)CCC1 OPCPFOCSMBITTL-UHFFFAOYSA-N 0.000 description 2
MOLKCHWJWVOZIX-UHFFFAOYSA-N 5-bromo-2-(piperidin-4-ylmethoxy)benzonitrile;hypochlorous acid Chemical compound ClO.N#CC1=CC(Br)=CC=C1OCC1CCNCC1 MOLKCHWJWVOZIX-UHFFFAOYSA-N 0.000 description 2
VHZOAVYVFAFIAA-UHFFFAOYSA-N 5-bromo-2-(piperidin-4-ylmethoxy)pyridine;hydrochloride Chemical compound Cl.N1=CC(Br)=CC=C1OCC1CCNCC1 VHZOAVYVFAFIAA-UHFFFAOYSA-N 0.000 description 2
KBRGGSBEJZDZPC-UHFFFAOYSA-N 5-bromo-2-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridine Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(Br)C=N1 KBRGGSBEJZDZPC-UHFFFAOYSA-N 0.000 description 2
UCJOGCXLFKVRHD-UHFFFAOYSA-N 5-bromo-2-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridine Chemical compound C1CN(CC(C)(C)C(F)(F)F)CCC1COC1=CC=C(Br)C=N1 UCJOGCXLFKVRHD-UHFFFAOYSA-N 0.000 description 2
208000024172 Cardiovascular disease Diseases 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
229940100389 Sulfonylurea Drugs 0.000 description 2
QCKFXHDNYRJAHL-UHFFFAOYSA-N [4-[(4-bromophenoxy)methyl]piperidin-1-yl]-[1-(trifluoromethyl)cyclobutyl]methanone Chemical compound C1CC(COC=2C=CC(Br)=CC=2)CCN1C(=O)C1(C(F)(F)F)CCC1 QCKFXHDNYRJAHL-UHFFFAOYSA-N 0.000 description 2
230000002411 adverse Effects 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
230000006229 amino acid addition Effects 0.000 description 2
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical class N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
SABBFVWMIYCPKH-UHFFFAOYSA-N ethyl 1-[1-(trifluoromethyl)cyclobutanecarbonyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)C1(C(F)(F)F)CCC1 SABBFVWMIYCPKH-UHFFFAOYSA-N 0.000 description 2
OTUUTWFORVRDSO-UHFFFAOYSA-N ethyl 4-[2-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoate Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(CC)(F)CC)C1=CC(=C(C=C1)C(=O)OCC)F OTUUTWFORVRDSO-UHFFFAOYSA-N 0.000 description 2
LZVXFJHSFFUWGF-UHFFFAOYSA-N ethyl 4-[3-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoate Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(CC)(F)CC)C1=CC(=C(C=C1)C(=O)OCC)F LZVXFJHSFFUWGF-UHFFFAOYSA-N 0.000 description 2
GPIKMXNVFPAFIE-UHFFFAOYSA-N ethyl 4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoate Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)OCC)C=C1)F)(CC)F GPIKMXNVFPAFIE-UHFFFAOYSA-N 0.000 description 2
OMGMQHZEFUYIMV-UHFFFAOYSA-N ethyl 4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoate Chemical compound C1=C(F)C(C(=O)OCC)=CC=C1C(C=N1)=CC=C1OCC1CCN(CC(F)(CC)CC)CC1 OMGMQHZEFUYIMV-UHFFFAOYSA-N 0.000 description 2
RUJPPJYDHHAEEK-UHFFFAOYSA-N ethyl piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCNCC1 RUJPPJYDHHAEEK-UHFFFAOYSA-N 0.000 description 2
KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
150000002222 fluorine compounds Chemical group 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000003914 insulin secretion Effects 0.000 description 2
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
229960003105 metformin Drugs 0.000 description 2
238000000034 method Methods 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
BXQKHNPVDWEROF-HKBQPEDESA-N methyl (2S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxylate Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@](CCC1)(C(=O)OC)C BXQKHNPVDWEROF-HKBQPEDESA-N 0.000 description 2
KLIYVIWMYYVFON-YWEHKCAJSA-N methyl (2S,4R)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=CC=CC1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC)(CC)F KLIYVIWMYYVFON-YWEHKCAJSA-N 0.000 description 2
IVRQYBKUNSRKAS-BWKNWUBXSA-N methyl (2S,4R)-1-[4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC=1C=NC(=NC=1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)OC)C=C1)F)(CC)F IVRQYBKUNSRKAS-BWKNWUBXSA-N 0.000 description 2
IIHTYBPYSKMJSI-QPPBQGQZSA-N methyl (2S,4R)-1-[4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)OC)C=C1)F)(CC)F IIHTYBPYSKMJSI-QPPBQGQZSA-N 0.000 description 2
CVSVNNMQRCHDCY-HOFKKMOUSA-N methyl (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)OC)(CC)F CVSVNNMQRCHDCY-HOFKKMOUSA-N 0.000 description 2
BZSITJNWQMLPLM-UHFFFAOYSA-N methyl 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-2-fluorophenyl]benzoate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC(=C(C=C1)C1=CC=C(C=C1)C(=O)OC)F)(CC)F BZSITJNWQMLPLM-UHFFFAOYSA-N 0.000 description 2
PDRBBZDXWAATPO-UHFFFAOYSA-N methyl 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-3-fluorophenyl]-2-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC1=C(C=C(C=C1)C1=CC(=C(C=C1)C(=O)OC)F)F)(CC)F PDRBBZDXWAATPO-UHFFFAOYSA-N 0.000 description 2
ITAWMLAWTYGWRD-UHFFFAOYSA-N methyl 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-3-fluorobenzoate Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(C=2C(=CC(=CC=2)C(=O)OC)F)C=C1 ITAWMLAWTYGWRD-UHFFFAOYSA-N 0.000 description 2
FLOLBJULCHLQTO-UHFFFAOYSA-N methyl 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=CC(=C(C(=O)OC)C=C1)F)(CC)F FLOLBJULCHLQTO-UHFFFAOYSA-N 0.000 description 2
FIPIGPYNVLIBHM-UHFFFAOYSA-N methyl 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-3-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=C(C=C(C(=O)OC)C=C1)F)(CC)F FIPIGPYNVLIBHM-UHFFFAOYSA-N 0.000 description 2
DHYPHCRIGNCWCN-UHFFFAOYSA-N methyl 4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-3-fluorobenzoate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=C(C=C(C(=O)OC)C=C1)F)(CC)F DHYPHCRIGNCWCN-UHFFFAOYSA-N 0.000 description 2
BOWVQLFMWHZBEF-KTKRTIGZSA-N oleoyl ethanolamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCO BOWVQLFMWHZBEF-KTKRTIGZSA-N 0.000 description 2
XBXHCBLBYQEYTI-UHFFFAOYSA-N piperidin-4-ylmethanol Chemical compound OCC1CCNCC1 XBXHCBLBYQEYTI-UHFFFAOYSA-N 0.000 description 2
150000003053 piperidines Chemical class 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-M prolinate Chemical compound [O-]C(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-M 0.000 description 2
235000018102 proteins Nutrition 0.000 description 2
102000004169 proteins and genes Human genes 0.000 description 2
108090000623 proteins and genes Proteins 0.000 description 2
IDXKTTNFXPPXJY-UHFFFAOYSA-N pyrimidin-1-ium;chloride Chemical compound Cl.C1=CN=CN=C1 IDXKTTNFXPPXJY-UHFFFAOYSA-N 0.000 description 2
238000011160 research Methods 0.000 description 2
230000028327 secretion Effects 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
XTYQHIVJLVNWCM-UHFFFAOYSA-N tert-butyl 4-[(4-bromo-2-cyanophenoxy)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1COC1=CC=C(Br)C=C1C#N XTYQHIVJLVNWCM-UHFFFAOYSA-N 0.000 description 2
SVUVXYYRSOFJFX-UHFFFAOYSA-N tert-butyl 4-[(4-bromo-2-fluorophenoxy)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1COC1=CC=C(Br)C=C1F SVUVXYYRSOFJFX-UHFFFAOYSA-N 0.000 description 2
ZILOONBNCUULSU-UHFFFAOYSA-N tert-butyl 4-[(4-bromo-3-cyanophenoxy)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1COC1=CC=C(Br)C(C#N)=C1 ZILOONBNCUULSU-UHFFFAOYSA-N 0.000 description 2
WKTCVUDEBCGTIH-UHFFFAOYSA-N tert-butyl 4-[(4-bromo-3-fluorophenoxy)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1COC1=CC=C(Br)C(F)=C1 WKTCVUDEBCGTIH-UHFFFAOYSA-N 0.000 description 2
AUYNXTKHUQFAQZ-UHFFFAOYSA-N tert-butyl 4-[(4-bromophenoxy)methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1COC1=CC=C(Br)C=C1 AUYNXTKHUQFAQZ-UHFFFAOYSA-N 0.000 description 2
XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
YXPOMRMPBBKREE-PMERELPUSA-N (2S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxylic acid Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](CCC1)(C(=O)O)C YXPOMRMPBBKREE-PMERELPUSA-N 0.000 description 1
GDNKPELANYKENB-PMERELPUSA-N (2S)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxylic acid Chemical compound C(#N)C=1C=C(C=CC1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@](CCC1)(C(=O)O)C GDNKPELANYKENB-PMERELPUSA-N 0.000 description 1
JIKXUOVWQFKGSO-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)-2H-pyridin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(C=C1)OCC1=CCN(C=C1)CC(C)(C)F JIKXUOVWQFKGSO-NDEPHWFRSA-N 0.000 description 1
MHSGZPCVRPDODI-NDEPHWFRSA-N (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxylic acid Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)O)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C)(C)F MHSGZPCVRPDODI-NDEPHWFRSA-N 0.000 description 1
SFBUVAZNGQFFEC-MHZLTWQESA-N (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxylic acid Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)O)C)C=CC(=C1)C1=NC=C(C=N1)OCC1CCN(CC1)CC(C)(C)F SFBUVAZNGQFFEC-MHZLTWQESA-N 0.000 description 1
AGAJHYVERNFUIH-MHZLTWQESA-N (2S)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxamide Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)N)C)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F AGAJHYVERNFUIH-MHZLTWQESA-N 0.000 description 1
CYLBYUPMYQAPPJ-UTYLNVFUSA-N (2S,4R)-1-[1-fluoro-2-phenyl-5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]cyclohexa-2,4-diene-1-carbonyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC1(C(=CC=C(C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C1=CC=CC=C1)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)N)C CYLBYUPMYQAPPJ-UTYLNVFUSA-N 0.000 description 1
ZVLCJDAFGSJGCM-NLFFAJNJSA-N (2S,4R)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)O ZVLCJDAFGSJGCM-NLFFAJNJSA-N 0.000 description 1
UKVBNGYHMXQUFN-QPPBQGQZSA-N (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound C(#N)C=1C=C(C=CC=1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)O UKVBNGYHMXQUFN-QPPBQGQZSA-N 0.000 description 1
QZENWKBPOSMNPA-XXBNENTESA-N (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)O)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F QZENWKBPOSMNPA-XXBNENTESA-N 0.000 description 1
GZHQSBSMTWBPTQ-OFNKIYASSA-N (2S,4R)-1-[2-fluoro-4-[6-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)O)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C GZHQSBSMTWBPTQ-OFNKIYASSA-N 0.000 description 1
TVXOZZFOQXOBDM-GCJKJVERSA-N (2S,4R)-1-[2-fluoro-6-[4-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxylic acid Chemical compound FC1=C(C(=CC=C1)C1=CC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)O TVXOZZFOQXOBDM-GCJKJVERSA-N 0.000 description 1
BHVSIPDQDDZPQD-PIKZIKFNSA-N (2S,4R)-1-[3-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound FC=1C=C(C(=O)N2[C@@](C[C@H](C2)O)(C(=O)N)C)C=CC1C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F BHVSIPDQDDZPQD-PIKZIKFNSA-N 0.000 description 1
HMNGYUCNGVLHMH-DFXYEROKSA-N (2S,4R)-1-[6-(2-cyanophenyl)-2-fluoro-3-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]benzoyl]-4-hydroxy-2-methylpyrrolidine-2-carboxamide Chemical compound C(#N)C1=C(C=CC=C1)C=1C(=C(C(=CC=1)OCC1CCN(CC1)CC(C)(C)F)F)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)N)C HMNGYUCNGVLHMH-DFXYEROKSA-N 0.000 description 1
OPSZQWCADFKGDO-CPJSRVTESA-N (2S,4S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxylic acid Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)O OPSZQWCADFKGDO-CPJSRVTESA-N 0.000 description 1
DQILUKZTAKUPHV-NVQXNPDNSA-N (2S,4S)-4-fluoro-1-[2-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]benzoyl]pyrrolidine-2-carboxylic acid Chemical compound F[C@H]1C[C@H](N(C1)C(=O)C=1C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)O DQILUKZTAKUPHV-NVQXNPDNSA-N 0.000 description 1
UVELGIJTUQKAOV-GMAHTHKFSA-N (2S,4S)-4-fluoro-1-[4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]pyrrolidine-2-carboxylic acid Chemical compound F[C@H]1C[C@H](N(C1)C(C1=CC=C(C=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)=O)C(=O)O UVELGIJTUQKAOV-GMAHTHKFSA-N 0.000 description 1
WHFVDLFITXHHHR-UHFFFAOYSA-N 1-(trifluoromethyl)cyclobutane-1-carbaldehyde Chemical compound FC(F)(F)C1(C=O)CCC1 WHFVDLFITXHHHR-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
TXRXLKSQXOBRKG-UHFFFAOYSA-N 1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypiperidine-2-carboxylic acid Chemical compound OC1CCN(C(C1)C(O)=O)C(=O)C1=C(F)C=C(C=C1)C1=CN=C(OCC2CCN(CC3(CCC3)C(F)(F)F)CC2)C=N1 TXRXLKSQXOBRKG-UHFFFAOYSA-N 0.000 description 1
ZMNOVUCNSSBLIP-UHFFFAOYSA-N 1-[4-[(2-chloropyrimidin-5-yl)oxymethyl]piperidin-1-yl]-2-methylpropan-2-ol Chemical compound C1CN(CC(C)(O)C)CCC1COC1=CN=C(Cl)N=C1 ZMNOVUCNSSBLIP-UHFFFAOYSA-N 0.000 description 1
LCOAOYFSLDKGCQ-UHFFFAOYSA-N 1-[4-[(4-bromo-3-fluorophenoxy)methyl]piperidin-1-yl]-3,3,3-trifluoro-2,2-dimethylpropan-1-one Chemical compound CC(C)(C(=O)N1CCC(COC2=CC(F)=C(Br)C=C2)CC1)C(F)(F)F LCOAOYFSLDKGCQ-UHFFFAOYSA-N 0.000 description 1
GWMNIFPJOPITNX-UHFFFAOYSA-N 1-[4-[(5-bromopyridin-2-yl)oxymethyl]piperidin-1-yl]-2,2-difluorobutan-1-one Chemical compound CCC(F)(F)C(=O)N1CCC(COC2=NC=C(Br)C=C2)CC1 GWMNIFPJOPITNX-UHFFFAOYSA-N 0.000 description 1
JBHGCPGPIQQABC-UHFFFAOYSA-N 1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidine Chemical compound FC(C1(CCC1)CN1CCCCC1)(F)F JBHGCPGPIQQABC-UHFFFAOYSA-N 0.000 description 1
RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 1
KIYKHEOWZLJZSB-UHFFFAOYSA-N 2,5-dibromopyrazine Chemical compound BrC1=CN=C(Br)C=N1 KIYKHEOWZLJZSB-UHFFFAOYSA-N 0.000 description 1
ZHXUWDPHUQHFOV-UHFFFAOYSA-N 2,5-dibromopyridine Chemical compound BrC1=CC=C(Br)N=C1 ZHXUWDPHUQHFOV-UHFFFAOYSA-N 0.000 description 1
NFTMKHWBOINJGM-UHFFFAOYSA-N 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-4-[[4-(tetrazol-1-yl)phenoxy]methyl]-1,3-thiazole Chemical compound N1=CC(CC)=CN=C1N1CCC(C=2SC=C(COC=3C=CC(=CC=3)N3N=NN=C3)N=2)CC1 NFTMKHWBOINJGM-UHFFFAOYSA-N 0.000 description 1
QECGILOKGQPHKL-UHFFFAOYSA-N 2-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazine Chemical compound FC(C1(CCC1)CN1CCC(CC1)COC=1N=CC=NC=1)(F)F QECGILOKGQPHKL-UHFFFAOYSA-N 0.000 description 1
MTHLACDCQDJRLI-UHFFFAOYSA-N 2-bromo-5-(piperidin-4-ylmethoxy)pyrazine hydrochloride Chemical compound Cl.BrC1=NC=C(N=C1)OCC1CCNCC1 MTHLACDCQDJRLI-UHFFFAOYSA-N 0.000 description 1
YJPHXPHHNSOJKP-UHFFFAOYSA-N 2-bromo-5-(piperidin-4-ylmethoxy)pyrazine hypochlorous acid Chemical compound OCl.BrC1=NC=C(N=C1)OCC1CCNCC1 YJPHXPHHNSOJKP-UHFFFAOYSA-N 0.000 description 1
PMDDAAPZJRPYDC-UHFFFAOYSA-N 2-bromo-5-(piperidin-4-ylmethoxy)pyridine hydrochloride Chemical compound Cl.BrC1=NC=C(C=C1)OCC1CCNCC1 PMDDAAPZJRPYDC-UHFFFAOYSA-N 0.000 description 1
INVKSVUECOXGGF-UHFFFAOYSA-N 2-bromo-5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyrazine Chemical compound BrC1=NC=C(N=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F INVKSVUECOXGGF-UHFFFAOYSA-N 0.000 description 1
ZBKAPWWQVCDNKC-UHFFFAOYSA-N 2-bromo-5-[[1-(2-ethyl-2-hydroxybutyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(O)(CC)CC)CCC1COC1=CC=C(Br)C(C#N)=C1 ZBKAPWWQVCDNKC-UHFFFAOYSA-N 0.000 description 1
SURAVVTXNXKREE-UHFFFAOYSA-N 2-bromo-5-[[1-(2-hydroxy-2-methylpropyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(C)(O)C)CCC1COC1=CC=C(Br)C(C#N)=C1 SURAVVTXNXKREE-UHFFFAOYSA-N 0.000 description 1
IXJNUEMHAJZKFW-UHFFFAOYSA-N 2-bromo-5-hydroxybenzonitrile Chemical compound OC1=CC=C(Br)C(C#N)=C1 IXJNUEMHAJZKFW-UHFFFAOYSA-N 0.000 description 1
OHTQHZVNZWWYFD-UHFFFAOYSA-N 2-bromo-5-iodopyrazine Chemical compound BrC1=CN=C(I)C=N1 OHTQHZVNZWWYFD-UHFFFAOYSA-N 0.000 description 1
ASLNHXZYCOOQLE-UHFFFAOYSA-N 2-chloro-5-(piperidin-4-ylmethoxy)pyrimidine;hydrochloride Chemical compound Cl.C1=NC(Cl)=NC=C1OCC1CCNCC1 ASLNHXZYCOOQLE-UHFFFAOYSA-N 0.000 description 1
QLQNZKJTDKOGFL-UHFFFAOYSA-N 2-chloro-5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidine Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CN=C(Cl)N=C1 QLQNZKJTDKOGFL-UHFFFAOYSA-N 0.000 description 1
BOGPIHXNWPTGNH-UHFFFAOYSA-N 2-chloropyrimidin-5-ol Chemical compound OC1=CN=C(Cl)N=C1 BOGPIHXNWPTGNH-UHFFFAOYSA-N 0.000 description 1
OZVCLXLSBUSDSP-UHFFFAOYSA-N 2-fluoro-4-[2-fluoro-4-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]phenyl]benzoic acid Chemical compound FC1=C(C=CC(=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C)C1=CC(=C(C=C1)C(=O)O)F OZVCLXLSBUSDSP-UHFFFAOYSA-N 0.000 description 1
BDQHVJXOFGBCOY-UHFFFAOYSA-N 2-fluoro-4-[4-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]phenyl]benzoic acid Chemical compound FC=1C=C(C=CC=1C(=O)O)C1=CC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F BDQHVJXOFGBCOY-UHFFFAOYSA-N 0.000 description 1
NBTCNLWPYPNOMM-UHFFFAOYSA-N 2-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound FC1=C(C(=O)O)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F NBTCNLWPYPNOMM-UHFFFAOYSA-N 0.000 description 1
USSARQBXTLZMAM-UHFFFAOYSA-N 2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CC=C(C=2C=C(F)C(C(O)=O)=CC=2)N=C1 USSARQBXTLZMAM-UHFFFAOYSA-N 0.000 description 1
NQIAYAINDZIBBL-UHFFFAOYSA-N 2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]benzoic acid Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CN=C(C=2C=C(F)C(C(O)=O)=CC=2)N=C1 NQIAYAINDZIBBL-UHFFFAOYSA-N 0.000 description 1
WCJGWVYKZZXZAM-UHFFFAOYSA-N 2-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound FC1=C(C(=O)O)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C WCJGWVYKZZXZAM-UHFFFAOYSA-N 0.000 description 1
QSAKGUFWONHOEH-UHFFFAOYSA-N 2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC=C1C(N=C1)=CN=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 QSAKGUFWONHOEH-UHFFFAOYSA-N 0.000 description 1
WKDVXNRHDQJKKQ-UHFFFAOYSA-N 2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound FC1=C(C(=O)O)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F WKDVXNRHDQJKKQ-UHFFFAOYSA-N 0.000 description 1
BTEATLWLTQEQHJ-UHFFFAOYSA-N 2-fluoro-4-[6-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoic acid Chemical compound FC1=C(C(=O)O)C=CC(=C1)C=1C=NC(=CC=1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C BTEATLWLTQEQHJ-UHFFFAOYSA-N 0.000 description 1
USUFXHNMDLKHDT-UHFFFAOYSA-N 2-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC=C1C(C=N1)=CC=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 USUFXHNMDLKHDT-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical group Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
FGQWYERRSKPPBW-UHFFFAOYSA-N 3-[[4-[(2-chloropyrimidin-5-yl)oxymethyl]piperidin-1-yl]methoxy]pentan-3-ol Chemical compound ClC1=NC=C(C=N1)OCC1CCN(CC1)COC(CC)(CC)O FGQWYERRSKPPBW-UHFFFAOYSA-N 0.000 description 1
WPANOODANBHNST-UHFFFAOYSA-N 3-[[4-[(4-bromo-2-fluorophenoxy)methyl]piperidin-1-yl]methyl]pentan-3-ol Chemical compound C1CN(CC(O)(CC)CC)CCC1COC1=CC=C(Br)C=C1F WPANOODANBHNST-UHFFFAOYSA-N 0.000 description 1
XXENNSGNFUXKKU-UHFFFAOYSA-N 3-[[4-[(4-bromo-3-fluorophenoxy)methyl]piperidin-1-yl]methyl]pentan-3-ol Chemical compound BrC1=C(C=C(OCC2CCN(CC2)CC(CC)(CC)O)C=C1)F XXENNSGNFUXKKU-UHFFFAOYSA-N 0.000 description 1
KJGSCXKSQPGLBK-UHFFFAOYSA-N 3-[[4-[(4-bromophenoxy)methyl]piperidin-1-yl]methyl]pentan-3-ol Chemical compound C1CN(CC(O)(CC)CC)CCC1COC1=CC=C(Br)C=C1 KJGSCXKSQPGLBK-UHFFFAOYSA-N 0.000 description 1
RQXTVCGOMFKAIW-UHFFFAOYSA-N 3-[[4-[(5-bromopyridin-2-yl)oxymethyl]piperidin-1-yl]methyl]pentan-3-ol Chemical compound C1CN(CC(O)(CC)CC)CCC1COC1=CC=C(Br)C=N1 RQXTVCGOMFKAIW-UHFFFAOYSA-N 0.000 description 1
JEVVMCLEPUZIHJ-UHFFFAOYSA-N 3-[[4-[(6-bromopyridin-3-yl)oxymethyl]piperidin-1-yl]methyl]pentan-3-ol Chemical compound BrC1=CC=C(C=N1)OCC1CCN(CC1)CC(CC)(CC)O JEVVMCLEPUZIHJ-UHFFFAOYSA-N 0.000 description 1
OBWJOBTVPNUBQP-UHFFFAOYSA-N 3-fluoro-4-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]benzoic acid Chemical compound FC1=CC(C(=O)O)=CC=C1C(C=C1)=CC=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 OBWJOBTVPNUBQP-UHFFFAOYSA-N 0.000 description 1
YSAKGDAEFIZMCX-UHFFFAOYSA-N 3-fluoro-4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound FC=1C=C(C(=O)O)C=CC=1C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C YSAKGDAEFIZMCX-UHFFFAOYSA-N 0.000 description 1
AZTTWGAPHCXCPU-UHFFFAOYSA-N 3-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoic acid Chemical compound FC1=CC(C(=O)O)=CC=C1C(N=C1)=CN=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 AZTTWGAPHCXCPU-UHFFFAOYSA-N 0.000 description 1
GDNIUQKYTKDUFK-UHFFFAOYSA-N 3-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound FC=1C=C(C(=O)O)C=CC=1C1=NC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F GDNIUQKYTKDUFK-UHFFFAOYSA-N 0.000 description 1
BJTAKAVLVVXYQC-UHFFFAOYSA-N 3-fluoro-4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoic acid Chemical compound FC1=CC(C(=O)O)=CC=C1C(C=N1)=CC=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 BJTAKAVLVVXYQC-UHFFFAOYSA-N 0.000 description 1
RYKZRKKEYSRDNF-UHFFFAOYSA-N 3-methylidenepentane Chemical compound CCC(=C)CC RYKZRKKEYSRDNF-UHFFFAOYSA-N 0.000 description 1
BPGPRVANUDRBTH-UHFFFAOYSA-N 4-[(4-bromo-2-fluorophenoxy)methyl]piperidine;hydrochloride Chemical compound Cl.FC1=CC(Br)=CC=C1OCC1CCNCC1 BPGPRVANUDRBTH-UHFFFAOYSA-N 0.000 description 1
ZKIFIIWPUQOQGR-UHFFFAOYSA-N 4-[(4-bromo-3-fluorophenoxy)methyl]-1-(2-ethyl-2-fluorobutyl)piperidine Chemical compound BrC1=C(C=C(OCC2CCN(CC2)CC(CC)(F)CC)C=C1)F ZKIFIIWPUQOQGR-UHFFFAOYSA-N 0.000 description 1
XJHKUTZTXAIOJX-UHFFFAOYSA-N 4-[2-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoic acid Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(CC)(F)CC)C1=CC(=C(C=C1)C(=O)O)F XJHKUTZTXAIOJX-UHFFFAOYSA-N 0.000 description 1
HNSCGEUYALGTLN-UHFFFAOYSA-N 4-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoic acid Chemical compound C1CN(CC(C)(F)C)CCC1COC(C=C1C#N)=CC=C1C1=CC=C(C(O)=O)C(F)=C1 HNSCGEUYALGTLN-UHFFFAOYSA-N 0.000 description 1
RYYQKZXQLZYKOX-UHFFFAOYSA-N 4-[3-cyano-4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoic acid Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(C=2C=C(F)C(C(O)=O)=CC=2)C=C1C#N RYYQKZXQLZYKOX-UHFFFAOYSA-N 0.000 description 1
CQBRNCCDFNRADY-UHFFFAOYSA-N 4-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-2-fluorobenzoic acid Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CC=C(C=2C=C(F)C(C(O)=O)=CC=2)C=C1C#N CQBRNCCDFNRADY-UHFFFAOYSA-N 0.000 description 1
DHSITBWAHHBVOG-UHFFFAOYSA-N 4-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]benzoic acid Chemical compound C1CN(CC(C)(F)C)CCC1COC1=CC=C(C=2C=CC(=CC=2)C(O)=O)C=C1C#N DHSITBWAHHBVOG-UHFFFAOYSA-N 0.000 description 1
XLYJUHPXGIVXEW-UHFFFAOYSA-N 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-2-fluorophenyl]benzoic acid Chemical compound C(C)C(CN1CCC(CC1)COC1=CC(=C(C=C1)C1=CC=C(C=C1)C(=O)O)F)(CC)F XLYJUHPXGIVXEW-UHFFFAOYSA-N 0.000 description 1
SDFHOGQRONIHID-UHFFFAOYSA-N 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]-3-fluorophenyl]-2-fluorobenzoic acid Chemical compound C(C)C(CN1CCC(CC1)COC1=C(C=C(C=C1)C1=CC(=C(C=C1)C(=O)O)F)F)(CC)F SDFHOGQRONIHID-UHFFFAOYSA-N 0.000 description 1
LNRQVFDYBHNTRL-UHFFFAOYSA-N 4-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-3-fluorobenzoic acid Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(C=2C(=CC(=CC=2)C(O)=O)F)C=C1 LNRQVFDYBHNTRL-UHFFFAOYSA-N 0.000 description 1
RVICWDMVSPXXDG-UHFFFAOYSA-N 4-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(C=C1)=CC=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 RVICWDMVSPXXDG-UHFFFAOYSA-N 0.000 description 1
SBILNNBDLIFUFV-UHFFFAOYSA-N 4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyrazin-2-yl]benzoic acid Chemical compound FC(CN1CCC(CC1)COC=1N=CC(=NC1)C1=CC=C(C(=O)O)C=C1)(C(F)(F)F)F SBILNNBDLIFUFV-UHFFFAOYSA-N 0.000 description 1
JLHVMILBMIQFFH-UHFFFAOYSA-N 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-2-fluorobenzoic acid Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(C=2C=C(F)C(C(O)=O)=CC=2)N=C1 JLHVMILBMIQFFH-UHFFFAOYSA-N 0.000 description 1
WEVSUFPNBCCTPS-UHFFFAOYSA-N 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]-3-fluorobenzoic acid Chemical compound C(C)C(CN1CCC(CC1)COC=1C=CC(=NC1)C1=C(C=C(C(=O)O)C=C1)F)(CC)F WEVSUFPNBCCTPS-UHFFFAOYSA-N 0.000 description 1
LUURXGRZTKYCCV-UHFFFAOYSA-N 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(C=2C=CC(=CC=2)C(O)=O)N=C1 LUURXGRZTKYCCV-UHFFFAOYSA-N 0.000 description 1
LGFRFYWNQVLOIJ-UHFFFAOYSA-N 4-[5-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]-2-fluorobenzoic acid Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CN=C(C=2C=C(F)C(C(O)=O)=CC=2)N=C1 LGFRFYWNQVLOIJ-UHFFFAOYSA-N 0.000 description 1
KDMNPZUHCCQKAP-UHFFFAOYSA-N 4-[5-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoic acid Chemical compound FC(C(CN1CCC(CC1)COC=1C=CC(=NC=1)C1=CC=C(C(=O)O)C=C1)(C)C)(F)F KDMNPZUHCCQKAP-UHFFFAOYSA-N 0.000 description 1
BPXXZACOZRITAT-UHFFFAOYSA-N 4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(N=C1)=CN=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 BPXXZACOZRITAT-UHFFFAOYSA-N 0.000 description 1
WVMAPKBNOMJLED-UHFFFAOYSA-N 4-[6-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-2-fluorobenzoic acid Chemical compound FC(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC(=C(C(=O)O)C=C1)F)(CC)F WVMAPKBNOMJLED-UHFFFAOYSA-N 0.000 description 1
UGHOKBVNPCAKAB-UHFFFAOYSA-N 4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]-3-fluorobenzoic acid Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=C(C=C(C(=O)O)C=C1)F)(CC)F UGHOKBVNPCAKAB-UHFFFAOYSA-N 0.000 description 1
YNDHRLMNMBULBH-UHFFFAOYSA-N 4-[6-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoic acid Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=N1)C1=CC=C(C(=O)O)C=C1)(CC)F YNDHRLMNMBULBH-UHFFFAOYSA-N 0.000 description 1
OYYPFECNMDNEJX-UHFFFAOYSA-N 4-[6-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyridin-3-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(C=N1)=CC=C1OCC1CCN(CC2(CCC2)C(F)(F)F)CC1 OYYPFECNMDNEJX-UHFFFAOYSA-N 0.000 description 1
RYVOZMPTISNBDB-UHFFFAOYSA-N 4-bromo-2-fluorophenol Chemical compound OC1=CC=C(Br)C=C1F RYVOZMPTISNBDB-UHFFFAOYSA-N 0.000 description 1
RMYOGXPGIDWJLU-UHFFFAOYSA-N 4-bromo-3-fluorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C(F)=C1 RMYOGXPGIDWJLU-UHFFFAOYSA-N 0.000 description 1
MRQYTJXVULSNIS-UHFFFAOYSA-N 4-bromo-3-fluorophenol Chemical compound OC1=CC=C(Br)C(F)=C1 MRQYTJXVULSNIS-UHFFFAOYSA-N 0.000 description 1
GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
HHDQVBSXYDRQGD-UHFFFAOYSA-N 4-hydroxypyrrolidine-1,2-dicarboxylic acid Chemical compound OC1CC(C(O)=O)N(C(O)=O)C1 HHDQVBSXYDRQGD-UHFFFAOYSA-N 0.000 description 1
AYJRTVVIBJSSKN-UHFFFAOYSA-N 5-[4-[[6-(4-methylsulfonylphenyl)pyridin-3-yl]oxymethyl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(COC=3C=NC(=CC=3)C=3C=CC(=CC=3)S(C)(=O)=O)CC2)=N1 AYJRTVVIBJSSKN-UHFFFAOYSA-N 0.000 description 1
PKDOPQDERQNHFV-UHFFFAOYSA-N 5-bromo-2-[[1-(2,2-difluorobutyl)piperidin-4-yl]methoxy]pyridine Chemical compound BrC=1C=CC(=NC1)OCC1CCN(CC1)CC(CC)(F)F PKDOPQDERQNHFV-UHFFFAOYSA-N 0.000 description 1
GLEMFXKGTQDQRG-UHFFFAOYSA-N 5-bromo-2-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(F)(CC)CC)CCC1COC1=CC=C(Br)C=C1C#N GLEMFXKGTQDQRG-UHFFFAOYSA-N 0.000 description 1
RRCIMDZSRUCPAT-UHFFFAOYSA-N 5-bromo-2-[[1-(2-ethyl-2-hydroxybutyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(O)(CC)CC)CCC1COC1=CC=C(Br)C=C1C#N RRCIMDZSRUCPAT-UHFFFAOYSA-N 0.000 description 1
MHTMGIBVOQDHJB-UHFFFAOYSA-N 5-bromo-2-[[1-(2-hydroxy-2-methylpropyl)piperidin-4-yl]methoxy]benzonitrile Chemical compound C1CN(CC(C)(O)C)CCC1COC1=CC=C(Br)C=C1C#N MHTMGIBVOQDHJB-UHFFFAOYSA-N 0.000 description 1
PVCONXMDUZOPJH-UHFFFAOYSA-N 5-bromo-2-hydroxybenzonitrile Chemical compound OC1=CC=C(Br)C=C1C#N PVCONXMDUZOPJH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
201000004569 Blindness Diseases 0.000 description 1
PRFZCCPEOIOARB-UHFFFAOYSA-N C(C)C1=C(C=CC=C1F)C1=C(C=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C)F Chemical group C(C)C1=C(C=CC=C1F)C1=C(C=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C)F PRFZCCPEOIOARB-UHFFFAOYSA-N 0.000 description 1
NDYWSWDCOWRLOQ-UHFFFAOYSA-N CCN(CC)SN(CC)CC.F.F.F Chemical group CCN(CC)SN(CC)CC.F.F.F NDYWSWDCOWRLOQ-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
SHVNVDAGRUHWEQ-UHFFFAOYSA-N ClO.N1=CC=NC=C1 Chemical compound ClO.N1=CC=NC=C1 SHVNVDAGRUHWEQ-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
OBODXJMKYYLIFO-CZWSTGFNSA-N FC1(C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC Chemical compound FC1(C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC OBODXJMKYYLIFO-CZWSTGFNSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
208000013016 Hypoglycemia Diseases 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
QQBPLXNESPTPNU-KTKRTIGZSA-N N-oleoyldopamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NCCC1=CC=C(O)C(O)=C1 QQBPLXNESPTPNU-KTKRTIGZSA-N 0.000 description 1
208000008589 Obesity Diseases 0.000 description 1
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
108020004459 Small interfering RNA Proteins 0.000 description 1
208000006011 Stroke Diseases 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
229940123464 Thiazolidinedione Drugs 0.000 description 1
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
PATKIKBZVKGANX-UHFFFAOYSA-N [4-[(5-bromopyridin-2-yl)oxymethyl]piperidin-1-yl]-[1-(trifluoromethyl)cyclobutyl]methanone Chemical compound BrC=1C=CC(=NC1)OCC1CCN(CC1)C(=O)C1(CCC1)C(F)(F)F PATKIKBZVKGANX-UHFFFAOYSA-N 0.000 description 1
229960002632 acarbose Drugs 0.000 description 1
XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
229940022663 acetate Drugs 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000012190 activator Substances 0.000 description 1
239000000556 agonist Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
150000008052 alkyl sulfonates Chemical class 0.000 description 1
230000004075 alteration Effects 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
238000002266 amputation Methods 0.000 description 1
230000003178 anti-diabetic effect Effects 0.000 description 1
125000005228 aryl sulfonate group Chemical group 0.000 description 1
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
239000002585 base Substances 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
230000003915 cell function Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
230000034994 death Effects 0.000 description 1
231100000517 death Toxicity 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
GMLFPSKPTROTFV-UHFFFAOYSA-N dimethylborane Chemical compound CBC GMLFPSKPTROTFV-UHFFFAOYSA-N 0.000 description 1
GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
WJJMNDUMQPNECX-UHFFFAOYSA-N dipicolinic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=N1 WJJMNDUMQPNECX-UHFFFAOYSA-N 0.000 description 1
CRHWEIDCXNDTMO-UHFFFAOYSA-N ditert-butylphosphane Chemical compound CC(C)(C)PC(C)(C)C CRHWEIDCXNDTMO-UHFFFAOYSA-N 0.000 description 1
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
DNXMVVKWUOPZGW-UHFFFAOYSA-N ethyl 1-(3,3,3-trifluoro-2,2-dimethylpropanoyl)piperidine-4-carboxylate Chemical compound CCOC(=O)C1CCN(C(=O)C(C)(C)C(F)(F)F)CC1 DNXMVVKWUOPZGW-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
ZHOGHWVKKXUAPI-UHFFFAOYSA-N fluorooxy(phenyl)borinic acid Chemical compound FOB(O)C1=CC=CC=C1 ZHOGHWVKKXUAPI-UHFFFAOYSA-N 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
230000006870 function Effects 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000004280 healthy diet Nutrition 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
JOTCUKNVJXRSTH-HKBQPEDESA-N methyl (2S)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-2-methylpyrrolidine-2-carboxylate Chemical compound C(#N)C=1C=C(C=CC=1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@](CCC1)(C(=O)OC)C JOTCUKNVJXRSTH-HKBQPEDESA-N 0.000 description 1
QXDGTKYBWKODIQ-LJAQVGFWSA-N methyl (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxylate Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)OC)C)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C)(C)F QXDGTKYBWKODIQ-LJAQVGFWSA-N 0.000 description 1
KTFNTIGAGSESFH-NDEPHWFRSA-N methyl (2S)-1-[2-fluoro-4-[5-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]pyrimidin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxylate Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)OC)C)C=CC(=C1)C1=NC=C(C=N1)OCC1CCN(CC1)CC(C)(C)F KTFNTIGAGSESFH-NDEPHWFRSA-N 0.000 description 1
DWAZIAZSJKEDIS-NDEPHWFRSA-N methyl (2S)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-2-methylpyrrolidine-2-carboxylate Chemical compound FC1=C(C(=O)N2[C@@](CCC2)(C(=O)OC)C)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F DWAZIAZSJKEDIS-NDEPHWFRSA-N 0.000 description 1
YPPCCVNRWXKMCR-IHJSMJRJSA-N methyl (2S,4R)-1-[1-fluoro-2-[4-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]phenyl]cyclohexa-2,4-diene-1-carbonyl]-4-hydroxy-2-methylpyrrolidine-2-carboxylate Chemical compound FC1(C(=CC=CC1)C1=CC=C(C=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C(=O)N1[C@@](C[C@H](C1)O)(C(=O)OC)C YPPCCVNRWXKMCR-IHJSMJRJSA-N 0.000 description 1
PZIYLIBUFFZODZ-CZWSTGFNSA-N methyl (2S,4R)-1-[1-fluoro-2-phenyl-5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]cyclohexa-2,4-diene-1-carbonyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC1(C(=CC=C(C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F)C1=CC=CC=C1)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC PZIYLIBUFFZODZ-CZWSTGFNSA-N 0.000 description 1
MDFLKCXLFFLXKQ-RLWLMLJZSA-N methyl (2S,4R)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC MDFLKCXLFFLXKQ-RLWLMLJZSA-N 0.000 description 1
QXXCYOXNCZLPDQ-RDGATRHJSA-N methyl (2S,4R)-1-[2-[3-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound C(#N)C=1C=C(C=CC=1OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC QXXCYOXNCZLPDQ-RDGATRHJSA-N 0.000 description 1
SSZHTFLXNBPPAT-JPYJTQIMSA-N methyl (2S,4R)-1-[2-fluoro-4-[5-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]pyridin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)OC)C=CC(=C1)C1=NC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F SSZHTFLXNBPPAT-JPYJTQIMSA-N 0.000 description 1
OAKJGVQSMAGJJR-YKSBVNFPSA-N methyl (2S,4R)-1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)OC)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F OAKJGVQSMAGJJR-YKSBVNFPSA-N 0.000 description 1
YLQMOAJDCBAGCK-QPPBQGQZSA-N methyl (2S,4R)-1-[2-fluoro-4-[6-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]pyridin-3-yl]benzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC1=C(C(=O)N2[C@@H](C[C@H](C2)O)C(=O)OC)C=CC(=C1)C=1C=NC(=CC1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C YLQMOAJDCBAGCK-QPPBQGQZSA-N 0.000 description 1
YPVPMGBHMNLKLZ-CLOONOSVSA-N methyl (2S,4R)-1-[2-fluoro-6-[2-fluoro-4-[[1-(3,3,3-trifluoro-2,2-dimethylpropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC1=C(C=CC(=C1)OCC1CCN(CC1)CC(C(F)(F)F)(C)C)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC YPVPMGBHMNLKLZ-CLOONOSVSA-N 0.000 description 1
LGDIVHCLQSGTLD-XXBNENTESA-N methyl (2S,4R)-1-[2-fluoro-6-[4-[[1-(2,2,3,3,3-pentafluoropropyl)piperidin-4-yl]methoxy]phenyl]benzoyl]-4-hydroxypyrrolidine-2-carboxylate Chemical compound FC1=C(C(=CC=C1)C1=CC=C(C=C1)OCC1CCN(CC1)CC(C(F)(F)F)(F)F)C(=O)N1[C@@H](C[C@H](C1)O)C(=O)OC LGDIVHCLQSGTLD-XXBNENTESA-N 0.000 description 1
DSDQKWZDXVJAQM-LVXARBLLSA-N methyl (2S,4S)-1-[2-[2-cyano-4-[[1-(2-fluoro-2-methylpropyl)piperidin-4-yl]methoxy]phenyl]-6-fluorobenzoyl]-4-fluoropyrrolidine-2-carboxylate Chemical compound C(#N)C1=C(C=CC(=C1)OCC1CCN(CC1)CC(C)(C)F)C=1C(=C(C=CC=1)F)C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)OC DSDQKWZDXVJAQM-LVXARBLLSA-N 0.000 description 1
RYBVAFCFYDBBAS-YXWJGHJBSA-N methyl (2S,4S)-1-[2-[4-[[1-(2-ethyl-2-fluorobutyl)piperidin-4-yl]methoxy]phenyl]-1-fluorocyclohexa-2,4-diene-1-carbonyl]-4-fluoropyrrolidine-2-carboxylate Chemical compound C(C)C(CN1CCC(CC1)COC1=CC=C(C=C1)C=1C(CC=CC=1)(C(=O)N1[C@@H](C[C@@H](C1)F)C(=O)OC)F)(CC)F RYBVAFCFYDBBAS-YXWJGHJBSA-N 0.000 description 1
ADJGFSMEAPXQLW-IYSWYEEDSA-N methyl (2r,4r)-4-hydroxy-2-methylpyrrolidine-2-carboxylate Chemical compound COC(=O)[C@@]1(C)C[C@@H](O)CN1 ADJGFSMEAPXQLW-IYSWYEEDSA-N 0.000 description 1
YCYWAVUCBMJUPK-FJXQXJEOSA-N methyl (2s)-2-methylpyrrolidine-2-carboxylate;hydrochloride Chemical compound [Cl-].COC(=O)[C@]1(C)CCC[NH2+]1 YCYWAVUCBMJUPK-FJXQXJEOSA-N 0.000 description 1
ADJGFSMEAPXQLW-VDTYLAMSSA-N methyl (2s,4r)-4-hydroxy-2-methylpyrrolidine-2-carboxylate Chemical compound COC(=O)[C@]1(C)C[C@@H](O)CN1 ADJGFSMEAPXQLW-VDTYLAMSSA-N 0.000 description 1
SNNUJJOVUWILIG-UHFFFAOYSA-N methyl 1-[2-fluoro-4-[5-[[1-[[1-(trifluoromethyl)cyclobutyl]methyl]piperidin-4-yl]methoxy]pyrazin-2-yl]benzoyl]-4-hydroxypiperidine-2-carboxylate Chemical compound FC1=C(C(=O)N2C(CC(CC2)O)C(=O)OC)C=CC(=C1)C1=NC=C(N=C1)OCC1CCN(CC1)CC1(CCC1)C(F)(F)F SNNUJJOVUWILIG-UHFFFAOYSA-N 0.000 description 1
ZORHSASAYVIBLY-UHFFFAOYSA-N methyl 4-hydroxypyrrolidine-2-carboxylate Chemical compound COC(=O)C1CC(O)CN1 ZORHSASAYVIBLY-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
235000020824 obesity Nutrition 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
SRJOCJYGOFTFLH-UHFFFAOYSA-M piperidine-4-carboxylate Chemical compound [O-]C(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-M 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
108091006084 receptor activators Proteins 0.000 description 1
230000009467 reduction Effects 0.000 description 1
150000003335 secondary amines Chemical group 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
150000001467 thiazolidinediones Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
230000004584 weight gain Effects 0.000 description 1
235000019786 weight gain Nutrition 0.000 description 1
230000004580 weight loss Effects 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Diabetes (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Emergency Medicine (AREA)
Hematology (AREA)
Obesity (AREA)
Endocrinology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

ES14866648T 2013-11-26 2014-11-25 Derivados de amida para el agonista del GPR119 Active ES2731823T3 (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
KR20130144601		2013-11-26
PCT/KR2014/011356 WO2015080446A1 (en)	2013-11-26	2014-11-25	Amide derivatives for gpr119 agonist

Publications (1)

Publication Number	Publication Date
ES2731823T3 true ES2731823T3 (es)	2019-11-19

Family

ID=53199342

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES14866648T Active ES2731823T3 (es)	2013-11-26	2014-11-25	Derivados de amida para el agonista del GPR119

Country Status (20)

Country	Link
US (1)	US9776987B2 (da)
EP (1)	EP3074384B1 (da)
JP (1)	JP6182269B2 (da)
KR (1)	KR101700906B1 (da)
CN (2)	CN110028494A (da)
AU (1)	AU2014354488B2 (da)
BR (1)	BR112016011999A2 (da)
CA (1)	CA2930850C (da)
DK (1)	DK3074384T3 (da)
ES (1)	ES2731823T3 (da)
HR (1)	HRP20191246T1 (da)
HU (1)	HUE045926T2 (da)
MX (1)	MX366297B (da)
NZ (1)	NZ720304A (da)
PH (1)	PH12016500980B1 (da)
PL (1)	PL3074384T3 (da)
PT (1)	PT3074384T (da)
RU (1)	RU2642429C2 (da)
TR (1)	TR201908098T4 (da)
WO (1)	WO2015080446A1 (da)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA3173731A1 (en)	2020-02-28	2021-09-02	Kallyope, Inc.	Gpr40 agonists
CN116323608A (zh)	2020-05-19	2023-06-23	卡尔优普公司	Ampk活化剂
EP4172162A4 (en)	2020-06-26	2024-08-07	Kallyope, Inc.	AMPK ACTIVATORS

Family Cites Families (25)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5109002A (en)	1989-09-08	1992-04-28	Du Pont Merck Pharmaceutical Company	Antipsychotic 1-cycloalkylpiperidines
ATE247612T1 (de)	2000-06-26	2003-09-15	Saudi Basic Ind Corp	Dimerisierung von olefinen
KR100849981B1 (ko)	2000-07-13	2008-08-01	메르크 파텐트 게엠베하	키랄 화합물 ｉ
ATE269856T1 (de)	2000-10-20	2004-07-15	Merck Patent Gmbh	Chirale binaphtol-verbindungen
DE102004037515A1 (de)	2003-08-22	2005-03-17	Merck Patent Gmbh	Verfahren zur Herstellung von Aldehyden
CA2661371A1 (en)	2006-08-30	2008-03-06	Biovitrum Ab (Publ)	Pyrimidine compounds for treating gpr119 related disorders
CN101657471B (zh) *	2006-12-06	2013-07-03	史密丝克莱恩比彻姆公司	二环化合物及其作为抗糖尿病药的用途
BRPI0806498A2 (pt)	2007-01-04	2014-04-22	Prosidion Ltd	Agonistas gpcr piperidina
JP5489997B2 (ja)	2007-07-19	2014-05-14	シマベイセラピューティクス，インコーポレーテッド	糖尿病および代謝疾患の治療のためのＲＵＰ３またはＧＰＲｌ１９受容体のアゴニストとしてのＮ−アザ環状置換ピロール、ピラゾール、イミダゾール、トリアゾールおよびテトラゾール誘導体
CA2697551C (en)	2007-09-20	2013-03-12	Irm Llc	Piperidine derivatives as modulators of gpr119 activity
WO2009106561A1 (en) *	2008-02-27	2009-09-03	Biovitrum Ab (Publ)	Pyrazine compounds for treating gpr119 related disorders
WO2009106565A1 (en)	2008-02-27	2009-09-03	Biovitrum Ab (Publ)	Agonists of gpr119
AU2009268527B2 (en)	2008-07-11	2012-11-01	Irm Llc	4-phenoxymethylpiperidines as modulators of GPR119 activity
WO2010048149A2 (en)	2008-10-20	2010-04-29	Kalypsys, Inc.	Heterocyclic modulators of gpr119 for treatment of disease
AR077642A1 (es)	2009-07-09	2011-09-14	Arena Pharm Inc	Moduladores del metabolismo y el tratamiento de trastornos relacionados con el mismo
AR077638A1 (es) *	2009-07-15	2011-09-14	Lilly Co Eli	Compuesto de (metanosulfonil -piperidin )-( alcoxi-aril) -tetrahidro- piridina , composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para el tratamiento de diabetes u obesidad
MX2012011631A (es) *	2010-04-06	2013-01-18	Arena Pharm Inc	Moduladores del receptor gpr119 y el tratamiento de trastornos relacionados con el mismo.
WO2011145718A1 (ja) *	2010-05-21	2011-11-24	田辺三菱製薬株式会社	新規ピロロ［２，３－ｄ］ピリミジン化合物
TW201202230A (en)	2010-05-24	2012-01-16	Mitsubishi Tanabe Pharma Corp	Novel quinazoline compound
CN102432598A (zh) *	2010-09-29	2012-05-02	江苏恒瑞医药股份有限公司	三环化合物、其制备方法及其在医药上的应用
EP2643311A1 (en)	2010-11-26	2013-10-02	Lupin Limited	Bicyclic gpr119 modulators
WO2012077655A1 (ja) *	2010-12-07	2012-06-14	塩野義製薬株式会社	Ｇｐｒ１１９アゴニスト活性を有するスピロ誘導体
JP2014159376A (ja) *	2011-06-17	2014-09-04	Taisho Pharmaceutical Co Ltd	アザスピロアルカン化合物
BR112014031091A2 (pt)	2012-06-12	2017-08-22	Chong Kun Pharmaceutical Corp	Derivados de piperidina para agonista de gpr119
WO2013187464A1 (ja) *	2012-06-13	2013-12-19	日産自動車株式会社	車両の駆動力制御装置

2014
- 2014-11-25 HR HRP20191246TT patent/HRP20191246T1/hr unknown
- 2014-11-25 MX MX2016006904A patent/MX366297B/es active IP Right Grant
- 2014-11-25 ES ES14866648T patent/ES2731823T3/es active Active
- 2014-11-25 EP EP14866648.0A patent/EP3074384B1/en active Active
- 2014-11-25 CN CN201910451096.6A patent/CN110028494A/zh active Pending
- 2014-11-25 JP JP2016534127A patent/JP6182269B2/ja not_active Expired - Fee Related
- 2014-11-25 KR KR1020140164986A patent/KR101700906B1/ko not_active Expired - Fee Related
- 2014-11-25 RU RU2016125492A patent/RU2642429C2/ru active
- 2014-11-25 PL PL14866648T patent/PL3074384T3/pl unknown
- 2014-11-25 HU HUE14866648A patent/HUE045926T2/hu unknown
- 2014-11-25 PT PT14866648T patent/PT3074384T/pt unknown
- 2014-11-25 BR BR112016011999A patent/BR112016011999A2/pt active Search and Examination
- 2014-11-25 NZ NZ720304A patent/NZ720304A/en not_active IP Right Cessation
- 2014-11-25 TR TR2019/08098T patent/TR201908098T4/tr unknown
- 2014-11-25 AU AU2014354488A patent/AU2014354488B2/en not_active Ceased
- 2014-11-25 WO PCT/KR2014/011356 patent/WO2015080446A1/en not_active Ceased
- 2014-11-25 CN CN201480064763.0A patent/CN105873916B/zh not_active Expired - Fee Related
- 2014-11-25 US US15/039,226 patent/US9776987B2/en not_active Expired - Fee Related
- 2014-11-25 CA CA2930850A patent/CA2930850C/en not_active Expired - Fee Related
- 2014-11-25 DK DK14866648.0T patent/DK3074384T3/da active
2016
- 2016-05-26 PH PH12016500980A patent/PH12016500980B1/en unknown

Also Published As

Publication number	Publication date
AU2014354488A1 (en)	2016-06-09
EP3074384A1 (en)	2016-10-05
BR112016011999A2 (pt)	2017-08-08
PL3074384T3 (pl)	2019-09-30
EP3074384B1 (en)	2019-05-22
JP2016538296A (ja)	2016-12-08
HRP20191246T1 (hr)	2019-12-27
US9776987B2 (en)	2017-10-03
RU2642429C2 (ru)	2018-01-25
EP3074384A4 (en)	2017-04-19
TR201908098T4 (tr)	2019-06-21
KR101700906B1 (ko)	2017-01-31
RU2016125492A (ru)	2018-01-09
DK3074384T3 (da)	2019-07-15
NZ720304A (en)	2017-08-25
KR20150060573A (ko)	2015-06-03
MX2016006904A (es)	2016-10-28
CA2930850A1 (en)	2015-06-04
PH12016500980A1 (en)	2016-06-20
CN110028494A (zh)	2019-07-19
CN105873916B (zh)	2019-08-27
CN105873916A (zh)	2016-08-17
HUE045926T2 (hu)	2020-01-28
US20170129875A1 (en)	2017-05-11
PT3074384T (pt)	2019-07-10
AU2014354488B2 (en)	2017-08-24
WO2015080446A1 (en)	2015-06-04
JP6182269B2 (ja)	2017-08-16
CA2930850C (en)	2017-05-16
MX366297B (es)	2019-07-04
PH12016500980B1 (en)	2016-06-20

Publication	Publication Date	Title
EP2858986B1 (en)	2019-10-30	Piperidine derivatives as gpr119 agonists
CA3069544A1 (en)	2019-01-31	Compounds and methods for the targeted degradation of androgen receptor
JP7834830B2 (ja)	2026-03-24	アミノピリジン誘導体およびそれらの選択的ａｌｋ－２阻害剤としての使用
AU2014354488B2 (en)	2017-08-24	Amide derivatives for GPR119 agonist
KR20230017787A (ko)	2023-02-06	Gpr39 단백질의 길항제
AU2020414202B2 (en)	2024-01-04	Novel amino aryl derivative useful as diacylglycerol acyltransferase 2 inhibitor and use thereof
TWI434830B (zh)	2014-04-21	一級胺二醇二氮烯鎓雜環衍生物
EP3444237B1 (en)	2020-10-28	Iridinesulfonamide compound and use method thereof
AU2013275090B2 (en)	2016-05-12	Piperidine derivatives for GPR119 agonist
HK40007931A (en)	2020-06-05	Amide derivative, stereoisomer thereof or pharmaceutically acceptable salt thereof, and composition comprising the same
WO2025106910A1 (en)	2025-05-22	Degrader molecules targeting androgen receptor
HK1225034B (zh)	2020-05-29	用於gpr119激动剂的酰胺衍生物
TW202540107A (zh)	2025-10-16	Ｍ４陽性變構調節劑
HK1225034A1 (en)	2017-09-01	Amide derivatives for gpr119 agonist
HK1133875A1 (en)	2010-04-09	Pyridine[3,4-b]pyrazinones